Fluorescent and NMR sensitive pH indicators

Abstract

This invention relates to compositions and methods useful for measuring pH generally, and intracellular pH specifically, and, more particularly, to a new class of fluorescent and fluorinated (NMR sensitive) aromatic compounds having excitation emission wavelengths in the ultraviolet or or visible portions of the electromagnetic spectrum, useful as pH indicators, as well as fluorine containing analogs useful in NMR spectroscopic determinations.

What is claimed is: 
     
       1. A compound, comprising the formula: ##STR35## and salts thereof, wherein: R 0  -R 2  are selected independently from the group consisting of hydrogen, alkyl, aryl, substituted alkyl, substituted aryl, carboxyl, carboxyalkyl, substituted carboxyalkyl, heteroaryl, and substituted heteroaryl; R 3  -R 6  are selected independently from the group consisting of hydrogen, alkyl, aryl, substituted alkyl, substituted aryl, ether, thioether, substituted amino, halogen, heteroaryl, substituted heteroaryl, carboxyl, carboxyalkyl, substituted carboxyalkyl and amido; and   X 1  is selected from the group consisting of oxygen, and NH; provided that: (a) R 0 , R 1  and R 2  are not all --CH 2  CO 2  H or --CH 2  CO 2  CH 3  when X 1  is oxygen, R 4  is fluorine or hydrogen, R 5  is hydrogen, fluorine or methyl, and R 3  and R 6  are hydrogen;   (b) R 0  and R 1  are not both --CH 2  CO 2  H when X 1  is oxygen, R 4  is fluorine and R 3 , R 5  and R 6  are hydrogen, and R 2  is --(CH 2 ) 2  O(CH 2 ) 2  N(CH 2  CO 2  H) 2  ;   (c) R 0  and R 1  are not both --CH 2  CO 2  H when X 1  is oxygen, R 3 , R 4 , R 5  and R 6  are fluorine or hydrogen, and R 2  is --(CH 2 ) 2  O(C 6  H 3  N(CH 2  CO 2  H) 2  F);   (d) R 0  and R 1  are not both --CH 2  CO 2  H or --CH 2  CO 2  CH 3  when X 1  is oxygen, R 4  is fluorine, R 5  is methyl, --C(CH 3 ) 2  CH 2  CO 2  H or --C(CH 3 ) 2  CH 2  CO 2  CH 3 , and R 3  and R 6  are hydrogen;   (e) R 0  and R 1  are not both --CH 2  CO 2  H or --CH 2  CO 2  CH 3  when X 1  is oxygen, R 4  is fluorine, R 5  -R 6  are hydrogen, and R 2  is an (8-amino-2-quinoline)methyl;   (f) R 0  and R 1  are not both --CH 2  CO 2  CH 2  C 6  H 5  when X 1  is oxygen, R 4  is fluorine, R 3 , R 5  and R 6  are hydrogen, and R 2  is --(CH 2 ) 2  O(CH 2 ) 2  N(CH 2  CO 2  CH 2  C 6  H 5 ) 2  ; and   (g) R 0  is not --C(CH 3 ) 2  CO 2  CH 3  or --C(CH 3 ) 2  CO 2  H when R 1  is hydrogen or methyl, X 1  is oxygen, R 4  is fluorine, and R 3 , R 5  and R 6  are hydrogen; and   (h) at least one of R 3  -R 6  is fluorine.     
     
     
       2. The compound of claim 1, wherein R 0  is selected from the group consisting of alkyl and substituted alkyl. 
     
     
       3. The compound of claim 2, wherein R 1  is selected from the group consisting of carboxyl, carboxyalkyl, and substituted carboxyalkyl. 
     
     
       4. The compound of claim 3, wherein said compound comprises the formula: ##STR36## 
     
     
       5. The compound of claim 4 wherein R 3  -R 6  are selected independently from the group consisting of hydrogen and fluorine. 
     
     
       6. The compound of claim 5, wherein said compound has the formula: ##STR37## 
     
     
       7. The compound of claim 5, wherein said compound has the formula: ##STR38##